Our laboratory is concerned with the regulation of glycogen phosphorylase and glucose homeostasis. We would like to explain this complex biochemical and physiological reaction in molecular terms. To do this we are studying various regulatory aspects of glycogen metabolism. There have been refinements in the crystal structure of glycogen phosphorylase at 2.1 A resolution using new and novel X-ray refinement procedures. We are currently investigating a number of exciting difference Fourier maps and doing model-building to show the effects on the enzyme structure and function when it binds numerous ligands. As we are working with rabbit liver and a cultured rat hepatocyte system, we are constantly monitoring possible in vivo effects based on our work studying the crystals and kinetics of the enzyme in solution. We have also learned how to activate the enzyme in crystals of rabbit enzyme which were grown in the presence of glucose as an inhibitor. This requires taking out the glucose and making numerous changes to the physical conditions as well as the buffer system. Using a number of tricks, we have been able to add activating ligands to our crystals, expanding the lattice so that it is able to support the enzyme in an active conformation. We plan to measure X-ray diffraction data on these crystals and solve the structure of the activated enzyme species. Steve Sprang has shown already that we may be able to use sophisticated crystallographic procedures to go from the inactive conformational state, atomic coordinates to atomic coordinates with the active conformational state. I feel this breakthrough in activating the enzyme in previously grown crystals to be extraordinarily promising in sorting out the physical chemistry of the activation of this molecule.